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Therapeutic potential of co-signaling receptor modulation in hepatitis B [scRNA-Seq]

GSE240036 Mus musculus (mouse) Single-cell RNA-seq 10 samples Submitted 2024/06/19 Platform GPL24247
At a glance

Single-cell RNA-seq · mouse · 10 samples

What it is
Single-cell RNA-seqGene activity measured in thousands of individual cells, so cell types can be told apart.
Organism
Mus musculus (mouse)
Samples
10 samples: 2 × CD8 T cells, HC_primed, d3, vs 2 × CD8 T cells, HC_primed, d5, vs 2 × CD8 T cells, HC_primed, d7, vs 2 × CD8 T cells, HC_primed, dGroups are read from the sample names, not from the paper. Check the list below.
Data you can get
A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Paper
Therapeutic potential of co-signaling receptor modulation in hepatitis BCell · 2024
Summary (written by the submitters)
Reversing CD8+ T cell dysfunction is crucial in therapeutic approaches to eliminate chronic hepatitis B virus (HBV) infection. However, the specific molecular targets for achieving this goal are not fully understood. In this study, we conducted a comprehensive analysis of the co-signaling receptors induced during hepatocellular priming and examined the trajectory and long-term fate of dysfunctional HBV-specific CD8+ T cells.
Read the full summary ↓
Our findings demonstrate that early during intrahepatic priming, HBV-specific CD8+ T cells selectively upregulate co-inhibitory receptors PD-1, CTLA-4, and LAG-3, as well as co-stimulatory receptors OX40, 4-1BB, and ICOS. While blocking the co-inhibitory receptors had no significant impact, activating 4-1BB and OX40, but not ICOS, transformed these cells into potent antiviral effectors. Prolonged antigenic stimulation of intrahepatically-primed dysfunctional T cells led to the development of a self-renewing, long-lived, heterogeneous population with a unique transcriptional profile that only partially overlaps with other forms of T cell hyporesponsiveness. This population consists of a dysfunctional progenitor or stem-like (TSL) population and two distinct dysfunctional tissue-resident memory (TRM) cell populations, which are hierarchically related. While 4-1BB expression is maintained across all populations, OX40 expression is limited to TSL cells. At later stages, only stimulation of 4-1BB, not OX40, conferred antiviral activity to HBV-specific CD8+ T cells. These findings highlight the therapeutic potential of co-signaling receptor modulation for chronic HBV infection and suggest that targeting all dysfunctional tissue-resident T cells, rather than solely the stem-like precursors, represents a promising strategy, distinguishing it from other conditions characterized by chronic antigenic stimulation.
Published in
Therapeutic potential of co-signaling receptor modulation in hepatitis B
Andreata F, Laura C, Ravà M et al. · Cell 2024 · PMID 38897196 · doi:10.1016/j.cell.2024.05.038
This dataset
Open GSE240036 in finder → Find more mouse RNA-seq datasets →
Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓
2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE240036_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓
3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: Single-cell studies usually ship their counts as 10x files (matrix.mtx, barcodes.tsv, features.tsv), an .h5 file, or an .rds / .h5ad object that Seurat or Scanpy can open. Look for those among the supplementary files.

Also filed as BioProject PRJNA1001959 and SRA study SRP453277. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 38897196) ↗
Study design
2 × CD8 T cells, HC_primed, d3, vs 2 × CD8 T cells, HC_primed, d5, vs 2 × CD8 T cells, HC_primed, d7, vs 2 × CD8 T cells, HC_primed, d

Supports a between-group comparison across 8 samples.

How we read this: 4 replicated groups read from 10 sample titles; they account for 8 of them. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study
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